Bioanalytical methodologies for clinical investigation of endocrine-disrupting chemicals: a comprehensive update

Bioanalysis ◽  
2021 ◽  
Author(s):  
Rajesh Pradhan ◽  
Siddhanth Hejmady ◽  
Rajeev Taliyan ◽  
Gautam Singhvi ◽  
Rajesh Khadgawat ◽  
...  

Endocrine-disrupting chemicals (EDCs) are xenobiotics that disrupt the endocrine system in humans at ecologically significant concentrations. Various substances are exposed to human health via routes including food, water, air and skin that result in disastrous maladies at low doses as well. Therefore EDCs need a meticulous strategy of analysis for dependable and consistent monitoring in humans. The management and risk assessment necessitate advancements in the detection methodologies of EDCs. Hyphenated MS-based chromatograph and other validated laboratory analysis methods are widely available and employed. Besides, in vitro bioassay techniques and biosensors are also used to conduct accurate toxicological tests. This article provides a revision of various bioanalytical detection methods and technologies for the clinical estimation of EDCs.

Author(s):  
Giuseppe Lisco ◽  
Vito Angelo Giagulli ◽  
Michele Iovino ◽  
Edoardo Guastamacchia ◽  
Giovanni De Pergola ◽  
...  

Background: Endocrine-disrupting chemicals (EDCs) are natural or synthetic compounds deriving from different human activities and are widely spread into the environment, contributing to indoor and outdoor pollution. EDCs may be conveyed by food and water consumption and skin, airways, placental, and breastfeeding. Upon entering the circulation, they can interfere with endocrine system homeostasis by several mechanisms. Aim: In this narrative review, the authors overviewed the leading mechanisms by which EDCs interact and disrupt the endocrine system, leading to possible human health concerns. Results: The leading mechanisms of EDCs-related toxicity have been illustrated in in vitro studies and animal models and may be summarized as follows: receptor agonism and antagonism; modulation of hormone receptor expression; interference with signal transduction in hormone-responsive cells; epigenetic modifications in hormone-producing or hormone-responsive cells; interference with hormone synthesis; interference with hormone transport across cell membranes; interference with hormone metabolism or clearance; interference with the destiny of hormone-producing or hormone-responsive cells. Discussion: Despite these well-defined mechanisms, some limitations do not allow for conclusive assumptions. Indeed, epidemiological and ecological studies are currently lacking and usually refer to a specific cluster of patients (occupational exposure). Methodological aspects could further complicate the issue since these studies could require a long time to provide useful information. The lack of a real unexposed group in environmental conditions, possible interference of EDCs mixture on biological results, and unpredictable dose-response curves for some EDCs should also be considered significant limitations. Conclusion: Given these limitations, specific observational and long-term studies are needed to identify at-risk populations for adequate treatment of exposed patients and effective prevention plans against excessive exposure to EDCs.


2019 ◽  
Vol 102 (1) ◽  
pp. 3-42 ◽  
Author(s):  
Telma Encarnação ◽  
Alberto ACC Pais ◽  
Maria G Campos ◽  
Hugh D Burrows

Endocrine disrupting chemicals are a group of pollutants that can affect the endocrine system and lead to diseases and dysfunctions across the lifespan of organisms. They are omnipresent. They are in the air we breathe, in the food we eat and in the water we drink. They can be found in our everyday lives through personal care products, household cleaning products, furniture and in children’s toys. Every year, hundreds of new chemicals are produced and released onto the market without being tested, and they reach our bodies through everyday products. Permanent exposure to those chemicals may intensify or even become the main cause for the development of diseases such as type 2 diabetes, obesity, cardiovascular diseases and certain types of cancer. In recent years, legislation and regulations have been implemented, which aim to control the release of potentially adverse endocrine disrupting chemicals, often invoking the precautionary principle. The objective of this review is to provide an overview of research on environmental aspects of endocrine disrupting chemicals and their effects on human health, based on evidence from animal and human studies. Emphasis is given to three ubiquitous and persistent groups of chemicals, polychlorinated biphenyls, polybrominated diphenyl ethers and organochlorine pesticides, and on two non-persistent, but ubiquitous, bisphenol A and phthalates. Some selected historical cases are also presented and successful cases of regulation and legislation described. These led to a decrease in exposure and consequent minimization of the effects of these compounds. Recommendations from experts on this field, World Health Organization, scientific reports and from the Endocrine Society are included.


2005 ◽  
Vol 24 (9) ◽  
pp. 431-437 ◽  
Author(s):  
Lennart Weltje ◽  
Frederick S vom Saal ◽  
Jörg Oehlmann

We discuss the similarities and differences of two types of effects that occur at low but not high doses of chemicals: hormesis and stimulation by oestrogenic endocrine-disrupting chemicals or xenoestrogens. While hormesis is a general phenomenon evoked by many compounds, oestrogenic stimulation occurs for specific chemicals that disrupt actions of endogenous oestrogen. Both types of phenomena can induce an inverted-U dose-response curve, from low-dose stimulation of response, and thus challenge current methods of risk assessment. Hormesis is generally thought to be caused by an over-reaction of detoxification mechanisms, which is considered an adaptive response that should protect an organism from subsequent stress. One view of the hormetic low-dose stimulatory response, i.e., increased performance, is that it is beneficial. In contrast, we propose that for manmade xenoestrogens this is never the case. This is demonstrated with examples for low doses of the oestrogenic environmental chemicals bisphenol A and octylphenol, and the oestrogenic drug-response curves is underestimated by the current threshold model used in risk assessment, and this is likely to apply to other endocrine-disrupting chemicals.


2020 ◽  
Vol 21 (4) ◽  
pp. 1519 ◽  
Author(s):  
Zi-Run Tang ◽  
Xue-Ling Xu ◽  
Shou-Long Deng ◽  
Zheng-Xing Lian ◽  
Kun Yu

Endocrine disrupting chemicals (EDCs) are exogenous substances that interfere with the stability and regulation of the endocrine system of the body or its offspring. These substances are generally stable in chemical properties, not easy to be biodegraded, and can be enriched in organisms. In the past half century, EDCs have gradually entered the food chain, and these substances have been frequently found in maternal blood. Perinatal maternal hormone levels are unstable and vulnerable to EDCs. Some EDCs can affect embryonic development through the blood-fetal barrier and cause damage to the neuroendocrine system, liver function, and genital development. Some also effect cross-generational inheritance through epigenetic mechanisms. This article mainly elaborates the mechanism and detection methods of estrogenic endocrine disruptors, such as bisphenol A (BPA), organochlorine pesticides (OCPs), diethylstilbestrol (DES) and phthalates (PAEs), and their effects on placenta and fetal health in order to raise concerns about the proper use of products containing EDCs during pregnancy and provide a reference for human health.


Endocrinology ◽  
2006 ◽  
Vol 147 (6) ◽  
pp. s25-s32 ◽  
Author(s):  
Derek V. Henley ◽  
Kenneth S. Korach

Abstract The term endocrine-disrupting chemicals is used to define a structurally diverse class of synthetic and natural compounds that possess the ability to alter various components of the endocrine system and potentially induce adverse health effects in exposed individuals and populations. Research on these compounds has revealed that they use a variety of both nuclear receptor-mediated and non-receptor-mediated mechanisms to modulate different components of the endocrine system. This review will describe in vitro and in vivo studies that highlight the spectrum of unique mechanisms of action and biological effects of four endocrine-disrupting chemicals–diethylstilbestrol, genistein, di(n-butyl)phthalate, and methoxyacetic acid–to illustrate the diverse and complex nature of this class of compounds.


2021 ◽  
Vol 11 ◽  
Author(s):  
Fritzie T. Celino-Brady ◽  
Darren T. Lerner ◽  
Andre P. Seale

Increasing industrial and agricultural activities have led to a disturbing increase of pollutant discharges into the environment. Most of these pollutants can induce short-term, sustained or delayed impacts on developmental, physiological, and behavioral processes that are often regulated by the endocrine system in vertebrates, including fish, thus they are termed endocrine-disrupting chemicals (EDCs). Physiological impacts resulting from the exposure of these vertebrates to EDCs include abnormalities in growth and reproductive development, as many of the prevalent chemicals are capable of binding the receptors to sex steroid hormones. The approaches employed to investigate the action and impact of EDCs is largely dependent on the specific life history and habitat of each species, and the type of chemical that organisms are exposed to. Aquatic vertebrates, such as fish, are among the first organisms to be affected by waterborne EDCs, an attribute that has justified their wide-spread use as sentinel species. Many fish species are exposed to these chemicals in the wild, for either short or prolonged periods as larvae, adults, or both, thus, studies are typically designed to focus on either acute or chronic exposure at distinct developmental stages. The aim of this review is to provide an overview of the approaches and experimental methods commonly used to characterize the effects of some of the environmentally prevalent and emerging EDCs, including 17 α-ethinylestradiol, nonylphenol, BPA, phthalates, and arsenic; and the pervasive and potential carriers of EDCs, microplastics, on reproduction and growth. In vivo and in vitro studies are designed and employed to elucidate the direct effects of EDCs at the organismal and cellular levels, respectively. In silico approaches, on the other hand, comprise computational methods that have been more recently applied with the potential to replace extensive in vitro screening of EDCs. These approaches are discussed in light of model species, age and duration of EDC exposure.


2001 ◽  
Vol 36 (2) ◽  
pp. 319-330 ◽  
Author(s):  
Mark Servos ◽  
Don Bennie ◽  
Kent Burnison ◽  
Philippa Cureton ◽  
Nicol Davidson ◽  
...  

Abstract A number of biological responses and multigenerational effects, mediated through the disruption of endocrine systems, have been observed in biota exposed to relatively low concentrations of environmental contaminants. These types of responses need to be considered within a weight of evidence approach in our risk assessment and risk management frameworks. However, including endocrine responses in an environmental risk assessment introduces a number of uncertainties that must be considered. A risk assessment of nonylphenol and nonylphenol polyethoxylates (NP/NPE) is used as a case study to demonstrate the sources and magnitude of some of the uncertainties associated with using endocrine disruption as an assessment endpoint. Even with this relatively well studied group of substances, there are substantial knowledge gaps which contribute to the overall uncertainties, limiting the interpretation within the risk assessment. The uncertainty of extrapolating from in vitro or biochemical responses to higher levels of organization or across species is not well understood. The endocrine system is very complex and chemicals can interact or interfere with the normal function of endocrine systems in a number of ways (e.g., receptors, hormones) which may or may not result in an adverse responses in the whole organism. Using endocrine responses can lead to different conclusions than traditional endpoints due to a variety of factors, such as differences in relative potencies of chemicals for specific endpoints (e.g., receptor binding versus chronic toxicity). The uncertainties can also be considerably larger and the desirability of using endocrine endpoints should be carefully evaluated. Endocrine disruption is a mode of action and not a functional endpoint and this needs to be considered carefully in the problem formulation stage and the interpretation of the weight of evidence.


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